Clinical significance of Akt2 in advanced pancreatic cancer treated with erlotinib

Eri Banno, Yosuke Togashi, Marco A. De Velasco, Takuro Mizukami, Yu Nakamura, Masato Terashima, Kazuko Sakai, Yoshihiko Fujita, Ken Kamata, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Akt2 is an isoform of Akt, and an association between Akt2 and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated the association between Akt2 expression as evaluated using immunohistochemistry and the outcome of patients with advanced PC who had received treatment with erlotinib (an EGFR-TKI). Although the difference was not significant, patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with erlotinib plus gemcitabine than those with low expression levels (P=0.16 and 0.19, respectively). In vitro, an Akt2-amplified PC cell line and Akt2-overexpressed cell lines exhibited resistance to anti-EGFR therapies, including erlotinib, but combined treatment with BYL719 (a PI3K inhibitor) cancelled this resistance. Our findings suggest that Akt2 might be associated with the resistance to anti-EGFR therapies, especially the use of erlotinib against PC, and that this resistance can be overcome by combined treatment with a PI3K inhibitor. Akt2 expression could become a predictive biomarker for erlotinib resistance in PC.

Original languageEnglish
Pages (from-to)2049-2058
Number of pages10
JournalInternational journal of oncology
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 2017
Externally publishedYes

Keywords

  • Akt2
  • Anti-EGFR therapy
  • Erlotinib
  • Pancreatic cancer
  • PI3K inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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